Viruses are implicated in a variety of animal and human diseases. Numerous approaches have been proposed to combat these pathogens which include, but are not limited to, herpesviruses 1 and 2 (HSV-1 and HSV-2), influenza viruses A, B and C (orthomyxoviruses), parainfluenza viruses 1-4, mumps virus (paramyxovirus), adenoviruses, respiratory syncytial virus, Epstein-Barr virus, rhinoviruses, human immunodeficiency viruses (HIV), polioviruses, coxsackieviruses, echoviruses, rubella virus, varicella-zoster virus, neurodermotropic virus, variola virus, cytomegalovirus, hepatitis A, B and non-A, non-B viruses, papoviruses and rabies virus.
One approach in the development of antiviral compounds has been to identify compounds which interfere with the normal viral metabolism of nucleosides. Because the structures of these compounds are usually closely related to nucleosides which occur naturally in the mammalian host, few have good activity against the virus without untoward side effects. Some of the few compounds having activity are very expensive to produce. Thus, there is a continuing need for new compounds which act to kill viruses, to inhibit viral replication or to block the pathogenic actions of viruses.
Known antiviral, antibacterial, anticancer and cardiovascular compounds which are closely related to or derivatives of nucleosides include those disclosed in the following references:
Ashton, U.S. Pat. No. 4,617,304, issued Oct. 14, 1986, discloses ((hydroxymethy)cyclopropyl)methyl)-substituted purine and pyrimidine analogs which are useful as antiviral agents.
Albrecht, U.S. Pat. Nos. 4,016,267 and 3,923,792, issued Apr. 5, 1977 and Dec. 2, 1975, respectively, disclose cyclopropyl-, cyclopropylmethyl- and cyclopentyl-substituted nucleoside analogs which are useful as antibacterial agents.
Kjellin, U.S. Pat. Nos. 4,644,001 and 4,548,818, issued Feb. 17, 1987 and Oct. 22, 1985, respectively, disclose cyclopropyl-, cyclobutyl- and cyclopentyl-substituted purine analogs which are useful for treating obstructive airway disease or cardiac disease.
Temple, J. Med. Chem. 5 866 (1962), discloses cyclopropyl-substituted purine analogs which are useful for treating human epidermal carcinoma.
Masoliver, Spanish Patent No. ES519898, published Mar. 16, 1984, discloses cyclopropyl-substituted purine analogs.
Tolman, U.S. Pat. No. 4,782,062, issued Nov. 1, 1988, discloses 9-((Z)-2-(hydroxymethyl)cyclobutylmethyl)-guanine as a viral thymidine kinase inhibitor.
Shimada, European Patent Application No. EP0291917, published Nov. 23, 1988, discloses oxetanocin and oxetanocin analogs.
Marquez, Medicinal Research Reviews, 6 1-40 (1986), discloses substituted-cyclopentyl nucleoside analogs.
None of the above-mentioned references disclose or suggest the compounds of the present invention.